Camptothecin (CPT, Formula 1) is a natural product isolated from Nyssaceae plant Camptotheca acuminata, which was introduced into clinical practice in the early 1970s due to its excellent anticancer activity, later, due to diarrhea, hemorrhagic cystitis and other serious side effects, the clinical trials were terminated.

Since the 1990s, a number of camptothecin derivatives have come into the market or entered into clinical studies successively, including 10-hydroxycamptothecin, 7-ethyl-10-hydroxycamptothecin, 9-nitrocamptothecin, 9-aminocamptothecin, irinotecan (CPT-11, Formula 2), topotecan and belotecan, exatecan, lurtotecan, diflomotecan, gimatecan, karenitecin, and so on. Among them, irinotecan has a very broad antitumor spectrum, and Phase I, II clinical study results show that the drug has a positive effect on chemotherapy-resistant tumors such as metastatic colorectal cancer, non-small cell lung cancer, ovarian cancer and cervical cancer, and also has a certain effect on gastric cancer, malignant lymphoma non-Hodgkin's lymphoma, breast cancer, small cell lung cancer, skin cancer, pancreatic cancer. It is now mainly used as an effective drug for the treatment of advanced colorectal cancer, and can still be effective for 5-FU resistant cases.

However, camptothecin derivatives, including irinotecan, have a good anticancer activity, but still have some shortcomings, such as a poor solubility in water, great toxic side effects. The common adverse reactions are anorexia, nausea, vomit, diarrhea, leukopenia and neutropenia, anemia and thrombocytopenia, alopecia and acetylcholine syndrome. Especially diarrhea is the most common, nearly 90% of the subjects have diarrhea, of which nearly 30% have severe diarrhea.
Polyethylene glycol modification technology is a new technology developed rapidly in recent years, which is linking polyethylene glycol after activation to a drug molecule or surface to form a prodrug, and when the polyethylene glycol-drug complex enters the body, it can slowly release the drug molecule thus to produce curative effect. The polyethylene glycol-modified drug molecules have the following advantages: 1, increased water solubility of drugs; 2, reduced toxicity; 3, extended cycle half-life of drugs, reduced medication times, improved patient compliance, improved quality of life, reduced treatment cost; 4, reduced enzyme degradation effect, improved bioavailability.
Polyethylene glycol modification technology has been applied in camptothecin derivatives, WO2005028539 reports a series of compounds in which a multi-branched polyethylene glycol is linked to irinotecan, currently, in which one drug named etirinotecan pegol (Formula 3) is undergoing Phase III clinical trials for the treatment of metastatic breast cancer and colorectal cancer in a number of countries.
WO2007081596 reports a series of compounds in which a polyethylene glycol is linked to 7-ethyl-10-hydroxycamptothecin (an active metabolite of irinotecan in vivo), currently, in which one drug named firtecan pegol is undergoing Phase II clinical trials for the treatment of breast cancer and colorectal cancer in a number of countries.
CN103083680 discloses a polyethylene glycol-amino acid oligopeptide-irinotecan conjugate as shown in formula (4) having antitumor activity for the treatment of colorectal cancer, ovarian cancer and lung cancer, etc.
There have been no reports of pharmaceutical compositions of polyethylene glycol-modified camptothecin derivatives for injection in the prior art.

In the prior art, the pharmaceutical composition of the camptothecin derivative is mostly a lyophilized preparation for injection, and CN103655491 reports a pharmaceutical composition of an irinotecan hydrochloride and a preparation method thereof, wherein the irinotecan hydrochloride is prepared into a lyophilized preparation, however, in the preparation process not only irinotecan hydrochloride and water for injection are used, lactose, ethanol and other additives are also used, which may not only increase the cost of product, more importantly, introduce substances that may affect the efficacy and produce side effects, resulting in uncertainty factors for the drug safety.
In addition, in the prior art, high molecular weight polyethylene glycol amino acid oligopeptides are linked to camptothecin derivative through ester bonds, the ester bonds have a poor stability, especially in a humid environment is easier to be hydrolyzed slowly and thus release the camptothecin derivative, which thereby affects the effect of polyethylene glycol modified drugs, and in the preparation, storage and use of injections, particularly lyophilized preparations for injection, contact with the humid environment is unavoidable, resulting in a slow degradation of the pharmaceutical composition of the polyethylene glycol-modified camptothecin derivative, which affects the drug stability.